Prediction of platinum-resistance patients of gastric cancer using bioinformatics

Lack of guidelines for personalized chemotherapy treatment after surgery has caused gastric cancer (GC) patients' unnecessary exposure to toxicity and the financial burden of chemotherapy treatments. In our study, we aimed to identify potential biomarkers to predict GC patients' susceptibility to platinum-based on Gene Expression Omnibus (GEO) data sets. A total of 603 differentially expressed genes (DEGs) were identified between platinum-resistant cell lines and platinum-sensitive cell lines based on the Cancer Cell Line Encyclopedia (CCLE) data sets. A total of 253 patients who had accepted radical gastrectomy were recruited, of which 97 received platinum-based chemotherapy and 156 were untreated. Three biomarkers (BRMS1, ND6, SRXN1) were then selected by univariate and multivariate Cox regression analysis to establish the predictive models using nomogram. Then this model was further validated through the GEO data set (GSE62254) which showed that this model could precisely predict the disease-free survival and overall survival of patients treated with platinum-based chemotherapy after surgery compared with untreated GC patients (P < 0.0001). This predictive model might provide helpful messages about the patients' susceptibility to platinum to guide personalized chemotherapy.     

RyR3 amplifies RyR1-mediated Ca(2+)-induced Ca(2+) release in neonatal mammalian skeletal muscle

The neonatal mammalian skeletal muscle contains both type 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane. An allosteric interaction between RyR1 and dihydropyridine receptors located in the plasma membrane mediates voltage-induced Ca(2+) release (VICR) from the sarcoplasmic reticulum. RyR3, which disappears in adult muscle, is not involved in VICR, and the role of the transiently expressed RyR3 remains elusive. Here we demonstrate that RyR1 participates in both VICR and Ca(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal muscle. Confocal measurements of intracellular Ca(2+) in primary cultured mouse skeletal myotubes reveal active sites of Ca(2+) release caused by peripheral coupling between dihydropyridine receptors and RyR1. In myotubes lacking RyR3, the peripheral VICR component is unaffected, and RyR1s alone are able to support inward CICR propagation in most cells at an average speed of approximately 190 microm/s. With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propagates at 2,440 microm/s. Because neonatal skeletal muscle lacks a well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uniform, and synchronous activation of Ca(2+) release throughout the cell body. Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of cell differentiation and muscle contraction.     

Metabolic response to feeding in the Chinese striped-necked turtle, Ocadia sinensis

We measured oxygen consumption in juvenile Chinese striped-necked turtles (Ocadia sinensis) after they ingested food, either as a single meal or as double meals, to examine the influence of meal type and feeding frequency on specific dynamic action (SDA). Temporal variation in oxygen consumption after feeding was evident in the ingesting turtles but not in the unfed control turtles. In the single-meal experiment, the peak metabolic rate and the integrated SDA response (the whole energetic cost for the processes of digestion) both did not differ between turtles ingesting mealworms and shrimps when the influence of variation in ingested energy was removed, and the time to reach peak metabolic rate was not affected by meal type and the amount of food ingested. Turtles in the double-meal experiment ingested more energy and hence had a prolonged duration of SDA response than did those in the single-meal experiment, but the integrated SDA response did not differ between both experimental treatments when the influence of variation in ingested energy was removed. Our results show that meal type and feeding frequency have important consequences on the SDA response of juvenile O. sinensis. As the integrated SDA response remained remarkably constant either between turtles ingesting different food or between turtles ingesting the same food but at different frequencies when the influence of variation in ingested energy was removed, we therefore conclude that the energetic cost associated with ingestion is primarily determined by energy content of food ingested in juvenile O. sinensis.     

Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time

Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses’ Health Study (n = 87,108 women, 1980–2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986–2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01–1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09–1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68–0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92–1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.     

Solution structure of the cytotoxic RNase 4 from oocytes of bullfrog Rana catesbeiana

Cytotoxic ribonucleases with antitumor activity are mainly found in the oocytes and early embryos of frogs. Native RC-RNase 4 (RNase 4), consisting of 106 residues linked with four disulfide bridges, is a cytotoxic ribonuclease isolated from oocytes of bullfrog Rana catesbeiana. RNase 4 belongs to the bovine pancreatic ribonuclease (RNase A) superfamily. Recombinant RC-RNase 4 (rRNase 4), which contains an additional Met residue and glutamine instead of pyroglutamate at the N terminus, was found to possess less catalytic and cytotoxic activities than RNase 4. Equilibrium thermal and guanidine-HCl denaturation CD measurements revealed that RNase 4 is more thermally and chemically stable than rRNase 4. However, CD and NMR data showed that there is no gross conformational change between native and recombinant RNase 4. The NMR solution structure of rRNase 4 was determined to comprise three alpha-helices and two sets of antiparallel beta-sheets. Superimposition of each structure with the mean structure yielded an average root mean square deviation (RMSD) of 0.72(+/-0.14)A for the backbone atoms, and 1.42(+/-0.19)A for the heavy atoms in residues 3-105. A comparison of the 3D structure of rRNase 4 with the structurally and functionally related cytotoxic ribonuclease, onconase (ONC), showed that the two H-bonds in the N-terminal pyroglutamate of ONC were not present at the corresponding glutamine residue of rRNase 4. We suggest that the loss of these two H-bonds is one of the key factors responsible for the reductions of the conformational stability, catalytic and cytotoxic activities in rRNase 4. Furthermore, the differences of side-chain conformations of subsite residues among RNase A, ONC and rRNase 4 are related to their distinct catalytic activities and base preferences.     

动脉内灌药,内支架安置双介入治疗十二指肠恶性梗阻

通过动脉内灌药,内支架安置双介入治疗提高对十二指肠恶性梗阻姑息性治疗的疗效。十二指肠恶性梗阻病例１４例,男５例,女９例,年龄２０－６９岁,经口安置自膨式十二指肠金属支架共１５枚,其中１２例在支架安置后定期行肿瘤供血动脉插管介入化疗,所有病例梗阻症状解除,２例未行动脉灌药治疗者分别于２个月及４个月死亡,１２例双介入者生存期明显延长,最短６月,最长已达一年,结论：双介入治疗能够姑息治疗疗效延长晚期瘤患